Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Hematology, Peking University First Hospital, Beijing, China.
Immun Inflamm Dis. 2022 Sep;10(9):e687. doi: 10.1002/iid3.687.
The C-C chemokine receptor 5 (CCR5) is mainly expressed in a variety of immune cells. It interacts with multiple chemokine ligands that mediate the trafficking and recruitment of effector cells toward sites of inflammation. CCR5 not only plays a critical role in cell growth, activation, differentiation, adhesion, and migration but also participates in the development of acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation.
This is a literature review article. The research design method is an evidence-based rapid review. The present discourse aim is first to scrutinize and assess the available literature on CCR5 and acute GVHD. Standard literature and database searches were implemented, gathered relevant material, and extracted information was then assessed.
CCR5 is a marker of GVHD effector cells, and CCR5 expression is elevated when acute GVHD occurs. CCR5 blockade with maraviroc in clinical trials results in a low incidence of acute GVHD. The immune mechanism includes that CCR5 blockade inhibits donor T cell migration and recruitment toward target organs, reduces the absolute numbers of donor T cells, is capable of slightly suppressing dendritic cell maturation, and reduces the percentage of Th1 and Th17 subsets. CCR5 blockade also inhibits internalization and activation of chemokines, inhibits proliferation and chemotaxis of T cells, and decreases the production of TNF-α and IFN-γ. In addition, there may be a form of crosstalk between CCR5 and CCR2. Inconsistently, infusion of CCR5 Tregs into lethally irradiated mice significantly increased the infiltration of CD4 and CD8 T cells into the liver, resulting in earlier and more severe GVHD.
This review indicates that CCR5 plays an important role in pathogenesis and development of acute GVHD. Elucidating its role in different immune cells will aid the development of targeted therapeutic treatments.
C-C 趋化因子受体 5（CCR5）主要表达于各种免疫细胞，与多种趋化因子配体相互作用，介导效应细胞向炎症部位的迁移和募集。CCR5 不仅在细胞生长、激活、分化、黏附和迁移中发挥关键作用，而且还参与异基因造血细胞移植后急性移植物抗宿主病（GVHD）的发生。
这是一篇文献综述文章，研究设计方法是基于证据的快速综述。本研究旨在首先仔细审查和评估 CCR5 与急性 GVHD 相关的现有文献。进行了标准文献和数据库检索，收集相关材料，然后评估提取的信息。
CCR5 是 GVHD 效应细胞的标志物，急性 GVHD 发生时 CCR5 表达上调。临床试验中用马拉维若阻断 CCR5 可降低急性 GVHD 的发生率。免疫机制包括 CCR5 阻断抑制供体 T 细胞向靶器官的迁移和募集，减少供体 T 细胞的绝对数量，能够轻度抑制树突状细胞成熟，并降低 Th1 和 Th17 亚群的比例。CCR5 阻断还抑制趋化因子的内化和激活，抑制 T 细胞增殖和趋化性，并减少 TNF-α 和 IFN-γ 的产生。此外，CCR5 和 CCR2 之间可能存在一种串扰形式。不一致的是，将 CCR5 Treg 输注到致死性照射的小鼠中，显著增加了 CD4 和 CD8 T 细胞向肝脏的浸润，导致更早和更严重的 GVHD。
本综述表明，CCR5 在急性 GVHD 的发病机制和发展中起重要作用。阐明其在不同免疫细胞中的作用将有助于开发靶向治疗方法。
